First Directional Measurement of Sub-MeV Solar Neutrinos with Borexino.

We report the measurement of sub-MeV solar neutrinos through the use of their associated Cherenkov radiation, performed with the Borexino detector at the Laboratori Nazionali del Gran Sasso. The measurement is achieved using a novel technique that correlates individual photon hits of events to the known position of the Sun. In an energy window between 0.54 to 0.74 MeV, selected using the dominant scintillation light, we have measured 10 887_{-2103}^{+2386}(stat)±947(syst) (68% confidence interval) solar neutrinos out of 19 904 total events. This corresponds to a ^{7}Be neutrino interaction rate of 51.6_{-12.5}^{+13.9} counts/(day·100 ton), which is in agreement with the standard solar model predictions and the previous spectroscopic results of Borexino. The no-neutrino hypothesis can be excluded with >5σ confidence level. For the first time, we have demonstrated the possibility of utilizing the directional Cherenkov information for sub-MeV solar neutrinos, in a large-scale, high light yield liquid scintillator detector. This measurement provides an experimental proof of principle for future hybrid event reconstruction using both Cherenkov and scintillation signatures simultaneously.

Improved Measurement of Solar Neutrinos from the Carbon-Nitrogen-Oxygen Cycle by Borexino and Its Implications for the Standard Solar Model.

We present an improved measurement of the carbon-nitrogen-oxygen (CNO) solar neutrino interaction rate at Earth obtained with the complete Borexino Phase-III dataset. The measured rate, R_{CNO}=6.7_{-0.8}^{+2.0} counts/(day×100 tonnes), allows us to exclude the absence of the CNO signal with about 7σ C.L. The correspondent CNO neutrino flux is 6.6_{-0.9}^{+2.0}×10^{8} cm^{-2} s^{-1}, taking into account the neutrino flavor conversion. We use the new CNO measurement to evaluate the C and N abundances in the Sun with respect to the H abundance for the first time with solar neutrinos. Our result of N_{CN}=(5.78_{-1.00}^{+1.86})×10^{-4} displays a ∼2σ tension with the "low-metallicity" spectroscopic photospheric measurements. Furthermore, our result used together with the ^{7}Be and ^{8}B solar neutrino fluxes, also measured by Borexino, permits us to disfavor at 3.1σ C.L. the "low-metallicity" standard solar model B16-AGSS09met as an alternative to the "high-metallicity" standard solar model B16-GS98.

Single organic molecules for photonic quantum technologies.

Isolating single molecules in the solid state has allowed fundamental experiments in basic and applied sciences. When cooled down to liquid helium temperature, certain molecules show transition lines that are tens of megahertz wide, limited by only the excited-state lifetime. The extreme flexibility in the synthesis of organic materials provides, at low costs, a wide palette of emission wavelengths and supporting matrices for such single chromophores. In the past few decades, their controlled coupling to photonic structures has led to an optimized interaction efficiency with light. Molecules can hence be operated as single-photon sources and as nonlinear elements with competitive performance in terms of coherence, scalability and compatibility with diverse integrated platforms. Moreover, they can be used as transducers for the optical read-out of fields and material properties, with the promise of single-quanta resolution in the sensing of charges and motion. We show that quantum emitters based on single molecules hold promise to play a key role in the development of quantum science and technologies.

Changes in motor function and brain cortex mitochondrial active oxygen species production in aged mice.

Neuronal ageing is a complex physiological process, associated to metabolic and motor changes. In this study, 3 and 17 months old male Swiss mice were used. Aged mice exhibited a significant reduction in motor performance and walking footprint pattern. Synaptosomes and mitochondrial fractions were isolated from mouse brain cortex. Active oxygen species and cardiolipin content were measured in both subcellular fractions. Synaptosomal acetylcholinesterase activity was measured in both animal age groups. Results showed that superoxide levels were 42.9% lower in synaptosomes from old mice as compared with young animals, while no changes were observed in non-synaptic mitochondria. Succinate-glutamate dependent H2O2 production rate was 27.5% decreased in non-synaptic mitochondria from aged mice. Cardiolipin content was 21% decreased in synaptosomes from 17-months old animals, while no changes were observed in non-synaptic mitochondria. Acetylcholinesterase activity decreased 16% in 17-months old mice, as compared with young animals. Age-related alterations in neuronal function could be associated with changes in active oxygen species at synapses, with parallel motor deficiencies.

"Shades of Gray" in pancreatic ductal adenocarcinoma: Reappraisals on resectability criteria: Debated indications for surgery in pancreatic cancer.

Pancreatic ductal adenocarcinoma is one of the leading causes of cancer-related deaths and, currently, surgery is the only curative treatment. Patients with borderline resectable pancreatic cancer (BRPC) can benefit from a multidisciplinary approach and R0 resection, and can achieve the same outcome as resectable patients treated with upfront surgery. However, the definition of BRPC changes according to different classifications with a heterogeneous distribution of patients, and it is thus difficult to compare clinical evidence. We performed a literature review to assess the most suitable classification of BRPC. Our review was conducted using the PubMed database. Only articles containing more than ten patients classified according to NCCN, MDACC or AHPBA/SSAT/SSO classifications were selected. A total of 16 studies were included in our analysis, and were grouped according to one of these three classifications. The total resection rate was 61.4%, with considerable differences between the groups (68.4% for NCCN, 54.9% for MDACC and 53.2% for AHPBA/SSO/SSAT). The total R0 resection rate was 90.1% (89.1% for NCCN, 92.5% for MDACC and 84% for AHPBA/SSO/SSAT). Of the three classifications, NCCN limits the use of confusing terms and uses restrictive criteria to define the most appropriate treatment for each subgroup. However, several reports have suggested that, even in the case of a limited disease, biological and clinical factors should be considered in order to classify patients as resectable. NCCN classification appears to be the classification that allows the highest percentage of patients with BRPC to achieve resection without reducing the R0 resection rate. The choice of therapy should not only be based on imaging results, but also on a wider clinical multidisciplinary evaluation.

Deficiencies in health-related quality-of-life assessment and reporting: a systematic review of oncology randomized phase III trials published between 2012 and 2016.

Quality of life (QoL) is a relevant end point and a topic of growing interest by both scientific community and regulatory authorities. Our aim was to review QoL prevalence as an end point in cancer phase III trials published in major journals and to evaluate QoL reporting deficiencies in terms of under-reporting and delay of publication. All issues published between 2012 and 2016 by 11 major journals were hand-searched for primary publications of phase III trials in adult patients with solid tumors. Information about end points was derived from paper and study protocol, when available. Secondary QoL publications were searched in PubMed. In total, 446 publications were eligible. In 210 (47.1%), QoL was not included among end points. QoL was not an end point in 40.1% of trials in the advanced/metastatic setting, 39.7% of profit trials and 53.6% of non-profit trials. Out of 231 primary publications of trials with QoL as secondary or exploratory end point, QoL results were available in 143 (61.9%). QoL results were absent in 37.6% of publications in the advanced/metastatic setting, in 37.1% of profit trials and 39.3% of non-profit trials. Proportion of trials not including QoL as end point or with missing QoL results was relevant in all tumor types and for all treatment types. Overall, 70 secondary QoL publications were found: for trials without QoL results in the primary publication, probability of secondary publication was 12.5%, 30.9% and 40.3% at 1, 2 and 3 years, respectively. Proportion of trials not reporting QoL results was similar in trials with positive results (36.5%) and with negative results (39.4%), but the probability of secondary publication was higher in positive trials. QoL is not included among end points in a relevant proportion of recently published phase III trials in solid tumors. In addition, QoL results are subject to significant under-reporting and delay in publication.

In vitro evaluation of Saccharomyces cerevisiae cell wall fermentability using a dog model.

Six Saccharomyces cerevisiae cell wall samples were tested by the in vitro gas production technique using dog faeces as inoculum. In particular, the substrates resulted from three different production processes (alcoholic_A, bakers_BA and brewers_BR) and were characterized by two different carbohydrates (mannans + glucans) concentrations nitrogen-free extract (NFE high and low). Gas production of fermenting cultures was recorded for 72 hr to estimate the fermentation profiles. The organic matter degradability (OMD), fermentation liquor pH, short-chain fatty acids (SCFA) and ammonia (NH3 ) productions were also measured. All substrates presented a high percentage of OMD (>92%) and moderate fermentability in terms of cumulative volume of gas related to incubated OM (OMCV >50 ml/g) and short-chain fatty acids production (>25 mmol/g), proving their functional properties. Comparing the substrates, it seems evident that the production process affects the chemical composition of the yeast cell wall in terms of crude protein, ether extract and ash content. Consequently, the in vitro fermentation process was significantly different among substrates for volume of gas, SCFA and ammonia production. Regarding the fermentation rate profiles, the production process influenced mainly the curve shape, whereas the NFE concentration affected the quantity of gas produced per hour. In particular, both S. cerevisiae_BR showed very high percentage of OM degradability, gas and SCFA productions and a fast fermentation process due to their high content of fermentable carbohydrates. On the contrary, both S. cerevisiae_BA yeast cell walls appeared to be less degradable and fermentable, probably due to their high content of ether extract. Regarding both S. cerevisiae_A, the high protein content of these substrates could explain the contrasting in vitro results (high degradability with low gas and SCFA production).

Nutritional management of search and rescue dogs.

Dogs used for search and rescue (SAR) may experience continuous micro-traumas that predispose them to skeletal disorders. The aim of the present study was to evaluate the effect of diet on osteo-articular apparatus in healthy SAR dogs. A total of sixteen SAR dogs were divided into two groups (low supplementation (LS) and high supplementation (HS)) and were fed for 3 months with two experimental diets, characterised by the same protein and energy density, but different in n-3 PUFA (6·2 v. 8·4 % of metabolisable energy), chondroitin sulfate (219·8 v. 989·0 mg/kg DM) and glucosamine (769·2 v. 1318·7 mg/kg DM) in the LS and HS groups, respectively. At recruitment all dogs showed no joint inflammation signs, except four that showed mild symptoms. Haematology and serum biochemistry were performed every 30 d. Joint status was scored by physical and lameness evaluations. The sampling effect analysis showed potential beneficial effects by a decrease in a specific marker of membrane integrity (creatine kinase; CK). Comparing groups, glucose was significantly higher and CK was significantly lower in the HS group; however, in both cases the levels of these parameters fell in the normal range. At the end of the experiment, erythrocytes, Hb and packed cell volume were significantly higher in the HS compared with the LS group. These could result in an improvement in dogs' performance, even if this aspect was not investigated in the present study. Concerning joint evaluation (pain on manipulation, lameness and range of motion), no statistically significant differences were detected between the groups and within the experimental period.

Productive performance and blood profiles of laying hens fed Hermetia illucens larvae meal as total replacement of soybean meal from 24 to 45 weeks of age.

The aim of the research was to study the effects of an insect meal from Hermetia illucens larvae (HILM) as complete replacement of soybean meal (SBM) on productive performance and blood profiles of laying hens, from 24 to 45 wk of age. A total of 108 24-week-old Lohmann Brown Classic laying hens was equally divided into 2 groups (54 hens/group, 9 replicates of 6 hens/group). From 24 to 45 wk of age, the groups were fed 2 different isoproteic and isoenergetic diets: the control group (SBM) was fed a corn-soybean meal based diet, while in the HILM group the soybean meal was completely replaced by Hermetia illucens larvae meal. Feed intake, number of eggs produced, and egg weight were recorded weekly along the trial. At 45 wk of age, blood samples were collected from 2 hens per replicate. The use of HIML led to a more favorable (P < 0.01) feed conversion ratio in hens but lay percentage, feed intake, average egg weight, and egg mass were higher (P < 0.01) in hens fed the SBM diet. Hens fed insect meal produced a higher percentage of eggs from small (S), medium (M), and extra-large (XL) classes (P < 0.01) than SBM, while the SBM group had a higher percentage of eggs from the large (L) class (P < 0.01). The levels of globulin and albumin to globulin ratio were, respectively, higher and lower (P < 0.05) in HILM than the SBM group. Cholesterol and triglycerides were higher (P < 0.05 and P < 0.01, respectively) in hens from SBM than in the HILM group. Blood levels of Ca were higher (P < 0.01) in hens fed insect meal, while creatinine was higher (P < 0.01) in blood of hens fed SBM. Hermetia illucens larvae meal can be a suitable alternative protein source for laying hens even if the complete replacement of soybean meal needs further investigation to avoid the negative effects on feed intake.

Expression and Localization of Aquaporin 4 and Aquaporin 5 along the Large Intestine of Colostrum-Suckling Buffalo Calves.

Aquaporins (AQPs) are membrane channel proteins that play a role in regulating water permeability in many tissues. To date, seven isoforms of AQPs have been reported in the gastrointestinal tract in different mammalian species. In contrast, both tissue distribution and expression of AQPs are unknown in the buffalo. The purpose of this study was to investigate the expression of both AQP4 and AQP5 mRNAs and their relative proteins in the large intestinal tracts of buffalo calves after colostrum suckling using reverse transcriptase polymerase chain reaction (RT-PCR), Western blotting and immunohistochemistry. Our results revealed a diversified tissue AQP4 and AQP5 immunolocalization accompanied by their highest expression in the tissues of colostrum-suckling buffalo calves confirmed by Western blotting. In particular, AQP4 was distributed along the endothelium and enterocytes while AQP5 in the endocrine cells. These findings provide direct evidence for AQP4 and AQP5 expression in the large intestine, suggesting that different AQPs collaborate functionally and distinctively in water handling during intestinal development, especially during the first period after delivery.

Test of Electric Charge Conservation with Borexino.

Borexino is a liquid scintillation detector located deep underground at the Laboratori Nazionali del Gran Sasso (LNGS, Italy). Thanks to the unmatched radio purity of the scintillator, and to the well understood detector response at low energy, a new limit on the stability of the electron for decay into a neutrino and a single monoenergetic photon was obtained. This new bound, τ≥6.6×10^{28} yr at 90% C.L., is 2 orders of magnitude better than the previous limit.

Effect of colostrum and milk on small intestine expression of AQP4 and AQP5 in newborn buffalo calves.

Functional studies indicate differences in newborn gastrointestinal morphology and physiology after a meal. Both water and solutes transfer across the intestinal epithelial membrane appear to occur via aquaporins (AQPs). Given that the physiological roles of AQP4 and AQP5 in the developing intestine have not been fully established, the objective of this investigation was to determine their distribution, expression and respective mRNA in the small intestine of colostrums-suckling buffalo calves by using immunohistochemistry, Western blot, and reverse transcriptase-PCR analysis. Results showed different tissue distribution between AQP4 and AQP5 with the presence of the former along the enteric neurons and the latter in the endocrine cells. Moreover, their expression levels were high in the ileum of colostrum-suckling buffalo calves. The data present a link between feeding, intestinal development and water homeostasis, suggesting the involvement of these channel proteins in intestinal permeability and fluid secretion/absorption during this stage of development after birth.

Yellow mealworm larvae (Tenebrio molitor, L.) as a possible alternative to soybean meal in broiler diets.

The aim of the study was to evaluate the feasibility of replacing soybean meal (SBM) with Tenebrio molitor larvae (TML) meal in broiler diets. A total of 80 30-d-old male Shaver brown broilers were divided into two groups fed on two isoproteic and isoenergetic diets differing for protein source (SBM vs. TML). Up to 62 d of age, body weight and feed intake were recorded weekly and body weight gain, feed conversion ratio (FCR), protein efficiency ratio (PER) and European efficiency factor (EEF) were calculated. At 62 d, blood samples were collected from 16 birds/group for evaluation of blood profiles. Feed intake was not different between groups considering the entire period of the trial. The FCR was more favourable in the TML than SBM group from 46 d of age and in the entire period of the trial (4.13 vs. 3.62). The PER was higher in the SBM than in the TML group (1.92 vs. 1.37) while the EEF was higher in broilers fed on the TML diet (132.6 vs. 156.2). Albumin-to-globulin ratio was higher in broilers fed on SBM than in the other group (0.44 vs. 0.30). aspartate aminotransferase and alanine aminotransferase were higher in TML than SBM (195.1 vs. 178.6 U/l and 82.07 vs. 46.71 U/l, respectively). Uric acid was higher in broilers fed on SBM than TML (5.40 vs. 4.16 mg/dl). TML did not affect feed intake and growth rate of broilers from 30 to 62 d of age when compared to an isoproteic and isoenergetic SBM diet, but FCR of the TML group was more favourable than that of the SBM group. The lowest albumin-to-globulin ratio in broilers fed on TML suggests a higher immune response, probably due to the prebiotic effects of chitin.

A compact ultranarrow high-power laser system for experiments with 578 nm ytterbium clock transition.

In this paper, we present the realization of a compact, high-power laser system able to excite the ytterbium clock transition at 578 nm. Starting from an external-cavity laser based on a quantum dot chip at 1156 nm with an intra-cavity electro-optic modulator, we were able to obtain up to 60 mW of visible light at 578 nm via frequency doubling. The laser is locked with a 500 kHz bandwidth to an ultra-low-expansion glass cavity stabilized at its zero coefficient of thermal expansion temperature through an original thermal insulation and correction system. This laser allowed the observation of the clock transition in fermionic (173)Yb with a <50 Hz linewidth over 5 min, limited only by a residual frequency drift of some 0.1 Hz/s.

Alcohol hangover induces mitochondrial dysfunction and free radical production in mouse cerebellum.

Alcohol hangover (AH) is defined as the temporary state after alcohol binge-like drinking, starting when ethanol (EtOH) is absent in plasma. Previous data indicate that AH induces mitochondrial dysfunction and free radical production in mouse brain cortex. The aim of this work was to study mitochondrial function and reactive oxygen species production in mouse cerebellum at the onset of AH. Male mice received a single i.p. injection of EtOH (3.8g/kg BW) or saline solution. Mitochondrial function was evaluated 6h after injection (AH onset). At the onset of AH, malate-glutamate and succinate-supported state 4 oxygen uptake was 2.3 and 1.9-fold increased leading to a reduction in respiratory control of 55% and 48% respectively, as compared with controls. Decreases of 38% and 16% were found in Complex I-III and IV activities. Complex II-III activity was not affected by AH. Mitochondrial membrane potential and mitochondrial permeability changes were evaluated by flow cytometry. Mitochondrial membrane potential and permeability were decreased by AH in cerebellum mitochondria. Together with this, AH induced a 25% increase in superoxide anion and a 92% increase in hydrogen peroxide production in cerebellum mitochondria. Related to nitric oxide (NO) metabolism, neuronal nitric oxide synthase (nNOS) protein expression was 52% decreased by the hangover condition compared with control group. No differences were found in cerebellum NO production between control and treated mice. The present work demonstrates that the physiopathological state of AH involves mitochondrial dysfunction in mouse cerebellum showing the long-lasting effects of acute EtOH exposure in the central nervous system.

Expression and Localization of Aquaporin-1 Along the Intestine of Colostrum Suckling Buffalo Calves.

Aquaporin-1 (AQP1), a six-transmembrane domain protein, belongs to a highly conserved group of proteins called aquaporins known to regulate permeability across cell membranes. Although the role of AQP1 has been extensively studied, its specific activity along the gastrointestinal tract in animals during early postnatal development is poorly known. This study investigates the expression of AQP1 mRNA and protein in the small and large intestine of water buffalo calves after colostrum ingestion using reverse transcription-polymerase chain reaction (RT-PCR), Western blotting, and cellular localization of AQP1 by immunohistochemistry. Our results revealed AQP1 immunoreactivity and the presence of the corresponding mRNA in all the examined tracts of the intestine but with a different cellular localization. Western blotting confirmed the presence of AQP1, with a more intense band in colostrum-suckling animals. These findings offer insights into AQP1 expression in the small and large intestine, suggesting its involvement in osmoregulation in gastrointestinal physiology particularly during the first week after birth in relation to specific maturation of intestinal structures.

Direct observation of coherent interorbital spin-exchange dynamics.

We report on the first direct observation of fast spin-exchange coherent oscillations between different long-lived electronic orbitals of ultracold 173Yb fermions. We measure, in a model-independent way, the strength of the exchange interaction driving this coherent process. This observation allows us to retrieve important information on the interorbital collisional properties of 173Yb atoms and paves the way to novel quantum simulations of paradigmatic models of two-orbital quantum magnetism.

Reading the phase of a Raman excitation with a multi-state atomic interferometer.

Atomic memories for flying photonic qubits are an essential ingredient for many applications like e.g. quantum repeaters. Verification of the coherent transfer of information from a light field to an atomic superposition is usually obtained using an optical read-out. In this paper we report the direct detection of the atomic coherence by means of atom interferometry. We experimentally verified both that a bichromatic laser field closing a Raman transition imprints a distinct, controllable phase on the atomic coherence and that it can be recovered after a variable time delay.